The mechanism by which capsular polysaccharides inhibit phagocytosis of encapsulated microorganisms is not well defined. The objective of this proposed research is to define the mechanism by which the capsular polysaccharide of Cryptococcus neoformans is able to inhibit phagocytosis of the yeast by macrophages. Proposed studies will (1) characterize the normal mechanisms that mediate phagocytosis of non-encapsulated isolates of the yeast; (2) analyze mechanisms by which the capsular polysaccharide can block these normal phagocytic mechanisms; and (3) examine the biophysical characteristics of the capsular surface that produce a failure in recognition by macrophages.